Diagnostics

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Colorectal Cancer Panel

The Colorectal Cancer Panel is a comprehensive next-generation sequencing (NGS) panel that analyzes genes associated with increased risks for hereditary colorectal cancer.

Colorectal cancer occurs frequently in the general population, with the average person’s lifetime risk of developing colorectal cancer being approximately 5% (SEERP). Although the majority of colorectal cancer is not related to heritable factors, in approximately 5-10% cases colorectal cancer is caused by a specific genetic change (Bogaert and Prenen, 2014). Individuals who carry these genetic changes may be at significantly increased risk of developing colorectal cancer in their lifetime. The majority of hereditary colorectal cancer is caused by mutations in the MLH1, MSH2, MSH6, PMS2, and EPCAM genes, which can lead to lifetime colorectal cancer risks of up to 82%, and other, rarer genes can cause similar cancer risks (Kohlmann and Gruber, 2004). Frequently, changes in genes that result in increased risks for colorectal cancer also predispose individuals to increased risks for other malignancies.

Included Disorders

This panel includes genes associated with:

  • Lynch syndrome (hereditary non-polyposis colorectal cancer)
  • Cowden syndrome
  • Familial adenomatous polyposis
  • Hereditary diffuse gastric cancer
  • Juvenile polyposis syndrome
  • MUTYH-associated polyposis
  • Peutz-Jeghers syndrome
  • Li-Fraumeni syndrome
  • Hereditary mixed polyposis syndrome
  • Muir-Torre syndrome

Inheritance

Hereditary colorectal cancer is typically inherited in an autosomal dominant manner, although several of the genes on this panel are associated with recessive genetic conditions:

  • MLH1, MSH2, PMS2, and MSH6 are associated with constitutional mismatch repair deficiency
  • MUTYH is associated with MUTYH-associated polyposis

Indications for Testing

  • A personal history of early colorectal cancer
  • A personal history of multiple primary cancers
  • A personal history of large numbers adenomatous or hamartomatous colonic polyps
  • A family history suggestive of a hereditary cancer syndrome, including multiple individuals on the same side of a family diagnosed with cancer, especially at ages below population averages
  • Risk assessment for asymptomatic family of members of proband with molecular diagnosis of a hereditary cancer syndrome

Methodology

Next-generation sequencing technology is used to test clinically relevant portions of each gene, including coding exons, adjacent flanking bases, and selected introns/noncoding variants. Pathogenic and likely pathogenic variants are confirmed by orthogonal methods. Copy number variants, including intragenic deletions and duplications are detected to a resolution of a single exon. To request analysis of a specific single exon copy number variant, please contact our Client Services team prior to ordering.

Included Genes (18)

APC AXIN2 BMPR1A CDH1 CHEK2 EPCAM
GREM1 MLH1 MSH2 MSH6 MUTYH PMS2
POLD1 POLE PTEN SMAD4 STK11 TP53

Additions to the Colorectal Cancer Panel:

Emerging evidence genes can also be added onto the comprehensive panel. These genes do not have a clear association with hereditary colorectal cancer, but emerging evidence suggests that they may play a role in disease pathogenesis.

Emerging Evidence (7):

ATM BLM BUB1B ENG FLCN GALNT12 MLH3

References:

  • Bogaert J, Prenen H. Molecular genetics of colorectal cancer. Annals of Gastroenterology. 2014;27(1):9-14.
  • Kohlmann W, Gruber SB. Lynch Syndrome. 2004 Feb 5 [Updated 2014 May 22]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1211/
  • Surveillance, Epidemiology, and End Results Program (SEERP). Cancer Stat Fact Sheets [Accessed April 20, 2017]. Available from: http://seer.cancer.gov/